| dc.description.abstract | Epilepsy is the fourth most common neurological condition accounting for almost 1% of the global burden of disease. Phenytoin is broadly used as a pharmacotherapeutic cornerstone to prevent and treat this affliction in all age groups. Nevertheless, the pharmacokinetic behavior of phenytoin is complicated and shows a high degree of inter-individual variability. In addition, adequate dosing is further hampered by its extensive (≈ 90%) and variable protein binding. Therefore, the general consensus is that the dosing of phenytoin should be individualized based on therapeutic drug monitoring (TDM), especially in critically ill patients and as a first-line drug with its unusual pharmacokinetics and high protein binding, the TDM of phenytoin, especially measurement of the remaining unbound/free fraction of phenytoin, a pharmacologically active form of phenytoin, should be done to help treating clinician. However, routinely, total serum concentration is used for monitoring phenytoin. Therefore, drug concentrations should be measured in better alternative specimens as compared to serum, such as Exhaled Breath Condensate (EBC) or urine, which reflect the free drug concentration and can be collected noninvasively. The aim of the present study is to compare the specimens (Cerebrospinal Fluid (CSF), serum, EBC, and urine) for measuring therapeutic levels of phenytoin and validate the potential use of EBC and/or urine as an alternative specimen for phenytoin TDM.
Methods: A total of 17 patients was recruited among patients receiving phenytoin for seizure prophylaxis after brain injury (due to head trauma or neurosurgeries) and had external ventricular drain (EVD) at the neurosurgery departments of Imam Reza Hospital, Tabriz, Iran. CSF, serum, urine, and EBC phenytoin concentrations were measured by High Performance Liquid Chromatography - tandem Mass Spectrometer (HPLC–MS/MS) in positive ionization mode. Eventually, the correlations between measured phenytoin concentrations in those biosamples and, moreover, between concentrations and patients' demographic characteristics were evaluated.
Results: Serum concentrations were not influenced by age or Body Mass Index (BMI). There was a strong and significant correlation between the phenytoin CSF and serum levels (r= 0.83, p=0.0005), between the serum and urine levels (r= 0.73, p=0.003), and between the CSF and urine levels (r= 0.64, p=0.013). | en_US |
